Researchers Create a Map of the Human Immune System

A team of researchers from the University of Pennsylvania’s Perelman School of Medicine have mapped what they say is the anatomic atlas of B cells in the human body, shedding light on how the immune system controls infections.

As part of the human immune system, white blood cells called B-lymphocytes — or B-cells – work with macrophages and T-lymphocytes to produce the antibodies needed to attack germs and fight infections. Macrophages essentially eat pathogens, leaving behind antigens that B-cells attack by producing antibodies. The B-cells and T-lymphocytes can recognize the germs they’ve already fought off and essentially remember how to fight them again; this is the basis for the mechanism behind vaccines, which expose the human body to enough of a pathogen to trigger the immune response and build up immunity. When the body naturally encounters the pathogen again, B-cells work through clonal expansion in tissues as a few precursor cells multiply in response to a recognized antigen.

In a new study published in the journal Nature Biotechnology, a team of researchers studied how B-cell clones are distributed throughout the body. Using human organs from six donors who had consented to use for both research and transplantation, the research team sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments. Nina Luning Prak, MD, PhD, the study’s senior author, explained in a recent press release that B-cell clone populations partition into two broad networks. “There are large networks in the gut (the jejunum, ileum, and colon) and different networks in blood-rich regions such as blood, bone marrow, spleen, and lung. We essentially discovered and mapped the B-cell clonal geography of the human body.”

In the study, funded by the National Institutes of Health and the Department of Education’s Graduate Assistance in Areas of National Need program, the research team genetically sequenced the part of the B-cell gene that helps create diverse antibodies, and then used new data analysis and visualizing tools to plot their findings in a map, which took more than two years to develop. The study team noted that B-cells fight infection locally to activate immunity nearby in specific tissues, and that this infection-fighting activity differs from tissue to tissue. In a notable finding, the researchers say that they observed more B-cells in the gastrointestinal tract, which is home to a highly diverse array of antibodies.

“Presumably, this is because the gut is one of the organs that is constantly bombarded by stimuli from the environment — whether the stimuli that drive these B-cell clones are derived from the microbiome or other pathogens is not yet known,” said Dr. Prak.

By creating what they say is effectively an anatomic atlas of the properties and tissue connections of the network of B-cell clonal lineages in the human body, the authors write that their findings can help inform future studies on tissue-based immunity, such as vaccine responses, infections, autoimmunity and cancer. Possible applications of the new map may help researchers monitor tissue-specific immune responses in the future, immune responses to vaccines, or inappropriate antibody responses to organ-specific autoimmune diseases.

Feature Picture: Colorized scanning electron micrograph of a B cell from a human donor. Feature Picture Source: NIAID / flickr / Creative Commons.